+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

A combination of spin diffusion methods for the determination of protein-ligand complex structural ensembles

, : A combination of spin diffusion methods for the determination of protein-ligand complex structural ensembles. Angewandte Chemie 54(22): 6511-6515

Structure-based drug design (SBDD) is a powerful and widely used approach to optimize affinity of drug candidates. With the recently introduced INPHARMA method, the binding mode of small molecules to their protein target can be characterized even if no spectroscopic information about the protein is known. Here, we show that the combination of the spin-diffusion-based NMR methods INPHARMA, trNOE, and STD results in an accurate scoring function for docking modes and therefore determination of protein-ligand complex structures. Applications are shown on the model system protein kinase A and the drug targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing of several ligands improves the reliability of the scoring function further. The new score allows in the case of sEH detecting two binding modes of the ligand in its binding site, which was corroborated by X-ray analysis.


PMID: 25877959

DOI: 10.1002/anie.201500671

Other references

Osterwalder, J.J.; Knoblauch, A., 1991: Randomized and controlled single-case study--a scientific method for individual and difficult therapy decisions in clinical practice exemplified with methotrexate use in asthma. For various reasons, optimal individual therapies cannot always be derived from monitored, large-scale random studies. This applies particularly to delicate decisions on the treatment of chronically ill patients. In such situations, random, contro...

Lavoipierre, M.M., 1970: A note on the sarcoptid mites of Primates. Journal of Medical Entomology 7(3): 376-380

Saftig, P.; Hunziker, E.; Everts, V.; Jones, S.; Boyde, A.; Wehmeyer, O.; Suter, A.; von Figura, K., 2000: Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice. Cathepsin K is a cysteine proteinase expressed predominantly in osteoclasts. Cathepsin K cleaves key bone matrix proteins and is believed to play an important role in degrading the organic phase of bone during bone resorption. Pycnodysostosis, an...

Takahashi, T., 2015: Direct evaluation of endosymbiotic status in Paramecium bursaria using a capillary flow cytometer. Cytometry. Part A 85(11): 911-914

Lederer R.J., 1976: The breeding populations of piscivorous birds of eagle lake. American Birds 30(3): 771

Anderson, A.S.; Levin, T.N.; Feldman, T., 1997: External jugular vein approach for percutaneous right ventricular biopsy. A technique of external jugular venous cannulation for right ventricular endomyocardial biopsy is described. This often under-used approach for venous access warrants consideration in patients at high risk for bleeding complications, pneumothorax,...

Zhanchiv, T., 1978: Types of hemo globin and amylase and their role in ecological genetic differentiation of yak and cattle populations. Hb and amylase polymorphisms were studied in Mongolian cattle and yak populations. Alleles HbA, HbB in Hb locus and alleles AmA, AmB, AmC in amylase locus were found. A relatively high frequency of HbA and AmA was detected in the mountain herds of...

Lucas, W.J., 1910: Scottish dragonfly records. Annals of Scottish Natural History, 162-165

Kempster, Aj, 1988: Market requirements and their relation to carcass quality. Beta agonists and their effects on animal growth and carcass quality edited by JP Hanrahan: 2

Litovchenko, I.N., 1982: Activity of adenylate kinase ec in blood of irradiated rats. Forward and reverse adenylate kinase reactions were studied in blood of rats 1, 3, 7, 15 and 30 days after total X-ray irradiation with a dose of 154.8 mC/kg (600 R) dose. Adenylate kinase (EC activity in leukocytes and erythrocytes is in...